13. Disturbances in the end-stage protein metabolism – hyperazotemias. Disturbances in purine metabolism – pathophysiology of gout and its complications · Pathophysiology · MU Plovdiv

DISTURBANCES IN THE END-STAGE PROTEIN METABOLISM - HYPERAZOTEMIA

Metabolic disorders, or inborn errors of metabolism, are inherited genetic disorders in which an individual is not able to metabolise a nutrient such as proteins
Protein and ammonia metabolism produces urea in the urea cycle → then removed from the blood by the kidneys
Proteins undergo deamination mostly in the liver and muscles so they can enter the Krebs cycle and then be used in gluconeogenesis and lipid synthesis
Bi-products of deamination are ammonia and urea

⭐ Azotemia - condition characterised by abnormally high levels of nitrogen containing compounds (e.g. urea, creatinine)
It is largely related to insufficient filtering of the blood by the kidneys
It can lead to uremia, acute kidney injury, and gout if not controlled

Flapping tremor
Can cause bleeding in GI tract
Cerebral edema
Decreases ATP production
Enzyme glutamate dehydrogenase catalyses oxidative deamination of glutamate → ammonia and alpha-ketoglutarate
The reaction is reversible
Higher concentrations of ammonia favours backwards formation of glutamate from alpha-ketoglutarate
This depletes mitochondrial pool of ketoglutarate → key intermediate in the citric acid cycle → decreased rate of ATP production
BCAA (leucine, isoleucine, valine) could take up NH3+ from glutamate and form succinyl-CoA which can proceed in the citric acid cycle